Histo: Vascular and Cardiac Pathology Flashcards
What is atherosclerosis?
A disease characterised by atheromatous deposits and fibrosis of the inner layer (tunica intima) of arteries
List some risk factors for atherosclerosis.
- Age
- Sex
- Genetics (familial hypercholesterolaemia)
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes mellitus
- Obesity
RFs have multiplicative effect
Outline the pathogenesis of atherosclerosis.
What is a fatty streak?
- Earliest change in atherosclerosis
- Lipid-filled foamy macrophages deposit in the intima
- No flow disturbance
NOTE: presence in pretty much everyone > 10 years old
What is an atherosclerotic plaque?
- Lesion composed of cells, lipid, matrix
- Causes local flow disturbance
What is critical stenosis?
- Point at which oxygen demand is greater than supply
- Occurs at around 70% occlusion
- Causes stable angina
List three types of acute plaque change.
- Rupture - exposes prothrombogenic plaque contents
- Erosion - exposes prothrombogenic subendothelial basement membrane
- Haemorrhage into plaque - increases size
In which patients does acute plaque change tend to happen?
Patients with mild-to-moderate atheroma (large plaques tend to be very stable)
List some features of vulnerable plaques.
- Large lipid core
- Thin fibrous cap
What is the leading cause of death worldwide for both sexes?
Ischaemic heart disease
List the possible presentations of ischaemic heart disease.
- Angina pectoris
- MI
- Chronic ischaemic heart disease with heart failure
- Sudden cardiac death
What degree of stenosis is required for:
- Chest pain precipitated by exercise
- Chest pain at rest
- 75% stenosis
- 90% stenosis
Where are the most clinically significant sites for atheromatous plaques within the coronary circulation?
- First few centimetres of the LAD and left circumflex
- Entire length of right coronary artery
What is angina pectoris?
- Transient ischaemia that does not produce myocyte necrosis
- Types: stable, unstable, prinzmetal (due to artery spasm)
What are the characteristics of stable angina?
- Precipated by exertion
- Relieved by rest
- No plaque disruption
What are the characteristics of unstable angina?
- Onset with less exertion or at rest
- Disruption of plaque
- May have superimposed thrombus
- Warning of impending infarction
What is a myocardial infarction?
Death of cardiac muscle due to prolonged ischaemia.
Outline the pathogenesis of myocardial infarction.
- Sudden change in plaque
- Platelet aggregation
- Vasospasm
- Coagulation
- Thrombus evolves
Outline the myocardial response to plaque rupture.
- Loss of contractility occurs within 60 seconds
- Therefore heart failure may precede myocyte death (i.e. patients could get an arrhythmia and die before any histological changes take place)
- Irreversible after 20-30 mins
Which arteries tend to be involved in myocardial infarction (in order of most to least frequent)?
- LAD - 50%
- RCA - 40%
- LCX - 10%
Describe the microscopic changes that take place in myocardial infarction.
- Under 6 hours - normal histology
- 6-24 hours - loss of nuclei + striations, homogenous cytoplasm, necrotic cell death
- 1-4 days - infiltration of PMNs then macrophages
- 5-10 days - removal of debris
- 1-2 weeks - granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
- Weeks to months - strengthening and decellularising the scar
What percentage of MI are asymptomatic, and in which patient groups are these more common?
- 10-15%
- Common in elderly and diabetics
What is reperfusion injury?
- Restoring blood flow to hypoxic tissue increases supply of oxygen which leads to increased production of ROS
- Oxidative stress, calcium overload and inflammation can cause further injury
- Arrhythmias are common
- It can cause stunned myocardium - reversible cardiac failure lasting several days
What is hibernating myocardium?
- Chronic sublethal ischaemia leads to lower metabolism in myocytes which can be reversed with vascularisation
List some complications of MI.
DARTH VADER
- Death
- Arrythmia
- Rupture
- Tamponade
- Heart failure
- Valve disease
- Aneurysm (ventricular)
- Dressler’s syndrome
- Embolism
- Recurrence
What is the 1-year mortality after an MI?
30%
What is chronic ischaemic heart disease?
- Progressive heart failure due to ischaemic myocardial damage
- Leads to hypertrophied, dilated LV
- Usually due to long-standing atherosclerosis
- Microscopic fibrosis
NOTE: there may be no prior infarction
What is sudden cardiac death?
- Unexpected death from cardiac causes in individuals without symptomatic heart disease or early (1hr) after the onset of symptoms
- Usually due to lethal arrhythmia
What are some underlying conditions that can cause sudden cardiac death?
IHD (90%)
- Acute myocardial ischaemia the usual trigger
- Leads to electrical instability of the conduction system
- This usually occurs at sites of old MI scars
Non-atherosclerotic cause (10%) - e.g. long QT
List some causes of heart failure.
- Ischaemic heart disease
- Valve disease
- Hypertension
- Myocarditis
- Cardiomyopathy
List some complications of heart failure.
- Sudden death
- Arrhythmias
- Systemic emboli
- Pulmonary oedema with superimposed infection
Outline the histology of heart failure.
- Dilated heart
- Scarring and thinning of the walls
- Fibrosis and replacement of ventricular myocardium
What are cardiomyopathies?
Intrinsic problems of the heart muscle
What is dilated cardiomyopathy?
Caused by progressive loss of myocytes leading to a dilated heart
List some causes of dilated cardiomyopathy.
- Idiopathic
- Genetic: familial, haemochromatosis
- Infection: post-viral myocarditis
- Toxins: alcohol, drugs (cocaine, doxorubicin)
What is hypertrophic cardiomyopathy?
- Thickening of the heart muscle
- Family history in 50% of cases
- Leads to ventricular outflow obstruction and arrhythmia
NOTE: some are associated with a specific abnormality in the beta-myosin heavy chain
What is restrictive cardiomyopathy?
Impaired ventricular compliance - diastolic dysfunction, near-normal systolic function
Causes:
- Amyloidosis
- Sarcoidosis
- Haemochromatosis
What is chronic rheumatic heart disease caused by?
Caused by immune cross-reactivity of group A streptococcal antigens and cardiac valves
Which valve is most commonly affected in rheumatic heart disease?
Mitral valve
What is the most common cause of aortic stenosis?
Aortic valve sclerosis - calcification (age-related)
List some causes of aortic regurgitation.
Valvular defect
- Congential bicuspid valve
- Age-related degeneration
- RHD
- Endocarditis
Aortic dilatation
- Dissection
- Chronic hypertension
- Connective tissue diease e.g. Marfan’s
- Aortitis e.g. syphilis
Which valves are most commonly affected by endocarditis?
- Left-sided valves (mitral > aortic)
- If IVDU, then tricuspid
What are the two different types of true aneurysms?
- Saccular
- Fusiform
